The thesis of this research is that the opioid drugs as well as many other drugs of abuse are used for their pleasurable effects and that a relevant animal model is the action of these drugs on the brain pathways that support intracranial self-stimulation. Many drugs of abuse will cause a lowering of the reinforcement threshold for self-stimulation. We propose that these effects reflect a functional increase in the sensitivity of the underlying neural systems, which may be directly related to the hedonic subjective effects of these compounds, and hence their abuse potential. The principal technique that we will use is the measurement of the threshold for intracranial self-stimulation in the rat. Various areas of the brain that support self-stimulation (rewarding) as well as those areas that are negatively reinforcing (aversive) will be investigated. In addition to the reinforcement threshold for self-stimulation we will study the effects of these drugs on the detection threshold for stimulation to both rewarding and aversive sites in the brain. The compounds to be studied will include the opiate agonist, partial agonist and antagonist as well as amphetamine, cocaine, phencyclidine and a number of putative endogenous peptides.